For dental and other applications there is a great need for self-filling tissue expanders with the capacity to be reshaped to fit the void by the surgeon at time of implantation. Akina recently completed an initial Phase II study using its hydrogel-based reshapable swelling tissue expanders (Restiex(R)). The study validated the function of Restiex to generate additional tissue of rat skin as well as of dog mucosa. Our subsequent dog study indicated that the properties of Restiex necessary for successful new tissue formation in dogs were very different from the properties identified from the rat study. Importantly, our current study has provided vital information on the Restiex properties required for successful insertion, expansion, and removal of the expander. This continuation Phase II study is to synthesize hydrogels possessing three critical properties identified from the dog studies. Controlling the swelling kinetics and expansion pressure is essential in preventing ischemia which causes necrosis and eruption of the expander. Controlling the mechanical strength is necessary for easy removal of the expander in one piece at the end of the expansion. The new hydrogel tissue expanders with tailor-made properties will be tested in our dog model for safety and effectiveness by Dr. Clark T. Barco, a co-investigator of this study. At the end of this Phase II renewal study, we will have the final formulation of Restiex expanders ready for clinical testing and commercialization. There are three specific aims of this Phase II renewal project: (1) to synthesize reshapable tissue expanders with controllable swelling kinetics, expansion pressure, and mechanical strength; (2) to validate safety and efficacy of tissue expanders in the intraoral dog model; and (3) to establish correlation between in vitro expander properties and in vivo performances. The renewed Phase II project will allow Akina to fully develop its hydrogel-based Restiex that has substantial advantages over current commercially available tissue expanders. No existing tissue expanders allow reshaping by a surgeon and also allow for the controlled swelling kinetics and expansion pressure. With these advantages, Akina's Restiex is expected to have immediate impact to the field. At the end of this renewal Phase II project, Akina will be able to produce safe and effective novel tissue expanders that are ready for human clinical trials.